Citations

LBA110 Background: There are limited data on COVID-19 in patients with cancer. We characterize the outcomes of patients with cancer and COVID-19 and identify potential prognostic factors. Methods: The COVID-19 and Cancer Consortium (CCC19) cohort study includes patients with active or prior hematologic or invasive solid malignancies reported across academic and community sites. Results: We included 1,018 cases accrued March-April 2020. Median age was 66 years (range, 18-90). Breast (20%) and prostate (16%) cancers were most prevalent; 43% of patients were on active anti-cancer treatment. At time of data analysis, 106 patients (10.4%) have died and 26% met the composite outcome of death, severe illness requiring hospitalization, and/or mechanical ventilation. In multivariable logistic regression analysis, independent factors associated with increased 30-day mortality were age, male sex, former smoking, ECOG performance status (2 versus 0/1: partially adjusted odds ratio (pAOR) 2.74, 95% CI 1.31-5.7; 3/4 versus 0/1: pAOR 5.34, 95% CI 2.44-11.69), active malignancy (stable/responding, pAOR 1.93, 95% CI 1.06-3.5; progressing, pAOR 3.79, 95% CI 1.78-8.08), and receipt of azithromycin and hydroxychloroquine. Tumor type, race/ethnicity, obesity, number of comorbidities, recent surgery, and type of active cancer therapy were not significant factors for mortality. Conclusions: All-cause 30-day mortality and severe illness in this cohort were significantly higher than previously reported for the general population and were associated with general risk factors as well as those unique to patients with cancer. Cancer type and treatment were not independently associated with increased 30-day mortality. Longer follow-up is needed to better understand the impact of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.

e12545 Background: Palbociclib(P), Ribociclib(R) and Abemaciclib(A) in combination with Endocrine therapy (ET) have demonstrated progression free survival (PFS) in patients with metastatic hormone receptor positive, HER2-negative breast cancer as compared to ET alone. In the absence of head to head clinical trials and to provide clinical guidance, we performed an indirect comparison for P, R and A using network Meta-Analysis (NMA). Methods: MEDLINE, EMBASE and the Cochrane Library were searched to identify RCTs comparing P+ET, R+ET, A+ ET vs ET alone. NMA for PFS and toxicity endpoints was conducted using a multivariate random-effects meta-regression, using a consistency model, as described by White and colleagues. We used a frequentist approach and provided a point estimate from the network and a 95% CI from the frequency distribution of the estimate. We also estimated the relative ranking of the different treatments for each outcome using the distribution of the ranking probabilities and the surface under the cumulative ranking curves (SUCRA). Risk of bias was assessed using Cochrane Collaboration tool. Results: 8 RCTs were identified including 4580 patients. Risk of bias was low. 5 RCTs tested CDK 4/6 inhibitors in endocrine naive and 2 in the refractory setting, while MONALESSA-3 included patients both with endocrine naive and endocrine resistant disease. In the endocrine naïve patients, PFS for P was similar when compared indirectly with R (HR, 0.95, 95% CI 0.67-1.35) or A (HR, 1.00, 95% CI 0.62-1.61). Similarly, indirect comparison between R vs A did not show any statistical significant (HR, 0.95, 95% CI 0.62-1.45). In endocrine refractory patients, P showed no difference when compared indirectly to A (HR 1.12, 95% CI 0.67-1.87) or R (HR 0.98, 95% CI 0.52-1.86). R vs A did not show any statistically significant PFS either (HR, 1.14, 95% CI 1.61-4.51). P was ranked first in terms of PFS in frontline setting (SUCRA of 70.5) while R ranked first in the refractory setting (SUCRA of 39.5). QT prolongation was reported for R only. P caused more neutropenia while A caused more fatigue, anemia and diarrhea, although the results were not statistically significant. Conclusions: The efficacy of using either palbociclib, ribociclib or abemaciclib in combination with ET was similar in terms of PFS in either endocrine naïve or resistant disease. Palbociclib causes more neutropenia, abemaciclib causes more fatigue, anemia and diarrhea while ribociclib causes QT prolongation.

Abstract Background: NPC is endemic to Asia and over 40% of cases harbor PIK3CA amplification. MK2206 is an allosteric AKT inhibitor with activity in NPC in vitro. Methods: Pts who had progressed after palliative chemotherapy (chemo) for metastatic or recurrent NPC, received oral MK-2206 at 200 mg on Days 1, 8, 15 & 22 of each 28-day cycle until disease progression. Plasma samples were collected at serial time points during cycle 1 for EBV DNA analysis, archived tumor samples were collected where feasible. The primary dual endpoints (2-stage design) consisted of RECIST-defined tumor response rate (RR) and 6-month (m) progression-free survival (PFS) rate. Secondary endpoints were overall survival (OS), PFS and adverse events (AEs). Results: Of the 21 pts enrolled, the median age was 47 years (range: 32-67), 91% were male, 81% had prior radiotherapy and 81% had > 1 prior line of palliative chemo. At the time of analysis, 20 out of 21 pts have ended treatment. The best responses were: 1 partial response (PR, 5%) lasting 4 ms; 10 stable disease (SD, 50%), 9 progressive disease (PD, 45%). The 6-m PFS rate was 38.9% (95% CI: 18.1-59.3%) and median PFS was 2.7 ms (95% CI: 0.9-7.2 ms). The 6-m OS rate was 67.9% (95% CI: 41.8-84.1%) and median survival has not been reached. In 7 pts who had SD more than or equal to 6 ms, the duration of treatment ranged from 6.4-13.9 ms. Of the 21 pts evaluable for AEs, 12 pts (57%) had at least one grade 3 AE [[Unable to Display Character: –]] macular rash (6 pts - 29%), dysphagia (2 pts - 10%), hyperglycemia (2 pts - 10%) (see Table 1). The tumor samples of 7 pts were analyzed by FISH; 3 showed PIK3CA amplification, including 1 pt with chromosome 3 polysomy. Amongst these pts, 1 had SD more than 6ms, 1 had SD more than 12 ms, and 1 is still on treatment. Pts who had SD less than 6 m or PD did not have PIK3CA amplification. Conclusions: MK2206 is well tolerated and has signs of activity in unselected pts with NPC. Preliminary results suggest that PIK3CA amplification may be related to prolonged disease stabilization from MK2206, and analysis for other PIK3CA gene alterations in more samples will be undertaken. Result of the plasma EBV DNA result will be presented. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B273. Citation Format: Brigette B. Ma, Boon Cher Goh, Wan Teck Lim, Eng Huat Tan, Gilberto de Lima Lopes, Edwin P. Hui, Ann D. King, Kwok Wai Lo, Herbert Loong, Leung Li, Nathan Foster, Michael Kam, Sing Fai Leung, Charles Erlichman, Anthony TC Chan. Multicenter Phase II study of MK-2206 in previously treated patients (pts) with recurrent and metastatic nasopharyngeal carcinoma (NPC): Mayo Clinic Phase II Consortium (Protocol: MC1079). [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B273.